Therapeutic Optimization in Crohn's Disease - Episode 15
Marla Dubinsky, MD: One of the things that we haven’t quite been able to pinpoint exactly to a patient is, what is your risk of surgery? Why are we so obsessed with minimizing complications and minimizing risk of surgery? I will tell you that we now understand some patients with Crohn’s disease have a very small segment, 10 to 15 cm of the small bowel, already damaged at diagnosis, which it’s not uncommon. It’s not the majority of patients, but a certain subset of patients, probably around 15%, who will present complicated at diagnosis. And so, if indeed there’s a subset of patients who already have scar tissue, and it’s a short segment, surgery up front and then treatment in the post-operative prevention setting is a much better strategy.
I often talk to patients, and it’s a lot easier to fight a downhill battle, which would be taking the disease out, resecting the patient, performing anastomosis—meaning primarily put back together—and then choosing our treatment. Our medicines work a lot better in a prevention mode than in an activation mode. And so, that’s always a conversation we have for those patients who I’m suspecting should go to surgery upfront.
But patients are really scared, and they believe that their whole goal is to prevent surgery. That’s another miscommunication between patients and physicians, that surgery could be amazing in the right patient population. If indeed surgery is the outcome we’re trying to prevent in a patient who doesn’t need surgery up front, let’s take that 80% or so of patients who present without strictures and fistulas, and our goal is to not reach the endpoint, and we have that time to really work together, the idea is that if the complication rate in first year is 17% and half of those patients would go to surgery, you’re dealing with about 10% of patients who may have to have surgery in the first year.
And every year, it may be a cumulative 10%. Before the biologic era, 7 to 8 out of 10 patients with Crohn’s disease went to surgery over time because we did not have drugs that could heal the mucosa or bowel, or prevent bowel wall damage. We never had that before. So, we were used to saying, “Well, if you are 1 of those patients, once you scar, we’ll take it out, we’ll start over, and the cycle starts again.” But that’s why tying it all together, knowing the risk of developing complications that will result in surgery and intervening early, can prevent surgery. So, I think that surgery has a very important place and shouldn’t be looked at as a failure. It’s not the drugs that have failed. The bowel wall damage had already set in. There’s nothing you could do. There’s no miracle drug that was reversing the scar tissue.
That aspect of surgery and its role needs to be better communicated, because people are thinking that’s what they want to prevent. But in essence, it may be your first move. Understanding that a little surgery in Crohn’s is evolving is important as we understand what our therapies can and cannot do.
Stephen B. Hanauer, MD: Surgery is indicated in Crohn’s disease in several different situations. If there is a limited segment of disease that does not respond to medical therapy, then we can remove that and restore the patient’s quality of life. But most often, surgery in Crohn’s disease is for complications such as strictures that lead to obstructions, strategic fistulas that impact on symptoms and quality of life for individuals, or infectious complications such as an abscess. In addition, on occasion, patients with refractory colitis may actually need a colectomy in order to improve their quality of life and long-term wellbeing.
The key to surgery in Crohn’s disease is to limit the operation to the affected bowel. We don’t need extensive margins. Indeed, we can even open up a narrowed area with what’s known as stricturoplasty without even removing the bowel. So, gut-conserving therapy is really important from a surgical standpoint to minimize the amount of bowel that’s removed.
William J. Sandborn, MD: One important thing to think about is how the need for surgery might have shifted in recent years. The biologics were launched almost 20 years ago, infliximab in 1998 in the United States. So, as almost 2 decades have gone by, you could gradually see shifts in the need for surgery, delays in the need for surgery, and even lower surgery rates. There was quite a learning curve for using the biologics and understanding the idea that they will be most effective if you introduce them early in the disease course, if you want to prevent complications and the need for surgery that often comes out of those complications. So, I think that we’re at the end of the beginning in terms of what might be possible for reducing surgery rates. We’ve seen some reduction, and I anticipate that we will see more reduction in the years to come.
A question that will often be asked is how affecting surgery rates affects the overall outcomes of the disease. The way I think of surgery is that it’s the ultimate bowel destruction. You’re completely eliminating pieces of bowel, and so this can be a big deal. If you resect the ileocecal value, you set the patient up for bacterial overgrowth. With resection of the terminal ileum, the patients will get set up for bile acid diarrhea. If they have enough ileal resection, they get set up for fat malabsorption and malnutrition. All of these comorbidities, which are induced by surgery, end up being largely irreversible, just degrade the patient’s function, and introduce an element of disability. So, if you want the patient to be as healthy as possible, the trick is to get endoscopic healing and clinical remission before irreversible bowel damage is done and before surgery is required, so that you don’t get the bowel damage from surgery itself. I think that those treatment goals, which were quite difficult to achieve 20 years ago, have become increasingly feasible using earlier intervention and a treat-to-target strategy in late 2017.
Transcript edited for clarity.